PDF(Pubmed)
Abstract：
Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (n = 81) and mouse (n = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-glycosaminoglycans and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress impacts these PNN features discovered that although early-life stress increases WFL+ PNN density, the CS-glycosaminoglycan sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments.
摘要：
神经周网（PNN）是细胞外基质的浓缩亚型，在大脑中某些神经元周围形成网状覆盖物。PNN主要由来自凝集素家族的硫酸软骨素（CS）蛋白聚糖组成，这些蛋白聚糖由连接到核心蛋白的CS-糖胺聚糖（CS-GAG）侧链组成。CS二糖可以以具有不同硫酸化模式的各种亚型存在。文献表明CS二糖硫酸化模式可以影响PNN的功能及其标记。进行这项研究以表征成年人（n=81）和小鼠（n=19）大脑中的这种区域间CS二糖硫酸化模式差异。液相色谱串联质谱用于定量五种不同的CS二糖硫酸化模式，然后将其与使用紫藤花凝集素（WFL）的PNN免疫标记进行比较，以鉴定CS-GAG和抗聚集蛋白聚糖以鉴定CS蛋白聚糖。在健康的大脑中，确定了CS二糖硫酸化和单标记与双标记模式的显着区域和物种特异性差异。研究早期压力（ELS）如何影响这些PNN特征的二次分析发现，尽管ELS增加了WFLPNN密度，两种物种的CS-GAG硫酸化代码和单PNN标记与双PNN标记分布均不受影响。这些结果强调了传统研究中的PNN复杂性，强调在未来的实验中需要考虑它们的异质性。
